# Circulating Tumor Cells in Uveal Melanoma: Multi-Marker Detection and Association With Disease State

## TL;DR

This study explores the use of circulating tumor cells in uveal melanoma patients as a non-invasive way to monitor disease progression and treatment response.

## Contribution

The study introduces a multi-marker approach for detecting circulating tumor cells in uveal melanoma and shows its feasibility across disease stages.

## Key findings

- CTC detection rates were higher in metastatic patients compared to those with localized disease.
- CTC counts increased significantly during fractionated stereotactic radiotherapy.
- Baseline CTC counts were not associated with tumor size or molecular risk class.

## Abstract

Uveal melanoma (UM) is primarily treated with eye-sparing radiotherapy, leaving limited tumor tissue for molecular analysis. Circulating tumor cells (CTCs) may offer a minimally invasive alternative for genomic tumor profiling. This pilot study evaluated the feasibility of a multi-marker CTC capture approach in UM patients at diagnosis, during fractionated stereotactic radiotherapy (fSRT), and at metastatic progression.

Patients with localized or metastatic UM were prospectively enrolled. Peripheral blood samples were collected at baseline, during fSRT, and on detection of metastases. CTCs were captured and enumerated using a multi-marker approach and fluorescence microscopy.

A total of 76 patients were included: 68 with localized disease and eight with metastatic disease. Four patients presented initially with localized disease but developed metastasis during follow-up: for comparisons, only metastatic-stage samples were used, yielding 64 localized and 12 metastatic samples. CTCs were detected in 69.1% of patients with localized disease at baseline and in 83.3% of those with metastases. CTC counts were significantly higher in metastatic disease than in localized disease (median = 8 vs. 3; P = 0.010). Among patients undergoing fSRT, paired analysis showed a significant increase in CTC counts between day 3 and day 5 (median = 1 vs. 4; P = 0.007). No significant associations were observed between baseline CTC counts and tumor thickness, largest basal diameter, tumor volume, American Joint Committee on Cancer tumor stage, tumor location, or molecular risk class.

Multi-marker CTC detection in UM patients is feasible across disease stages. Increased CTC counts during fSRT may offer a window for molecular characterization. Larger studies with longitudinal blood sampling are needed to validate clinical and prognostic utility.